St. Catherine Creek National Wildlife Refuge extends from just below Natchez, MS southward to the Homochitto River in Adams County, Mississippi. It lies entirely west of U.S. Highway 61 and the west side of the refuge is bordered by 18 miles of the Mississippi River.

Natchez is the oldest settlement on the Mississippi River, with continuous inhabitants since 1700. The city is rich in history and world famous for its magnificent antebellum homes, which stand as living examples of another time and culture. Famous and infamous characters once frequented the gambling halls and bars of Natchez-Under-the-Hill and roamed the hills, bluffs and bayous surrounding the city. Jim Bowie was one notable denizen. And the infamous and murderous Harpe brothers terrorized travelers on the Natchez Trace which begins at Natchez and stretches all the way into Tennessee. River pirates abounded along the Mississippi River as well.

The wealthy and more refined citizenry lived on top of the bluffs in Natchez, where it was cooler with less mosquitos and other undesirable elements such as were found under the hill. Natchez was a busy and bustling port and commerce flowed freely. In fact, at one time, Natchez was home to more millionaires per-capita than any other city in the United States. The city was surrounded by sprawling plantations where cotton was king. After the heyday of the plantations faded into history, much of that land was bought and converted into deer and duck hunting clubs which continue today.

Today, the refuge manages a complete program of habitat management, wildlife management, fisheries management, wildlife research, and threatened and endangered species management. Public use opportunities include hunting, fishing, outdoor photography, hiking, wildlife observation and conservation education.